Abstracts

Rationale: Mutations in CHD2, which encodes the chromodomain-helicase-DNA-binding protein 2, have only recently been recognised as a cause of epileptic encephalopathy. We describe the clinical features of early childhood epileptic encephalopathy due to de novo mutations of CHD2 to determine if a recognisable electroclinical epilepsy syndrome could be identified. Methods: We analysed the history, MRI and video-EEG recordings of nine individuals with de novo CHD2 mutations and one with a de novo 15q26 deletion encompassing CHD2. Results: Seizures began at a mean of 26 months (12-42) with myoclonic seizures in all ten cases. 7 exhibited exquisite clinical photosensitivity; 6 self-induced with the television. Absence seizures occurred in 9 patients including typical (4), atypical (2) and absence seizures with eyelid myoclonias (4). Generalized tonic-clonic seizures occurred in 9/10 cases with a mean onset of 5.8 years. Convulsive and non-convulsive status epilepticus were later features (6/10, mean onset 9 years). Tonic (40%) and atonic seizures (30%) also occurred. In 3 cases an unusual seizure type, the atonic-myoclonic-absence was captured on video. A phenotypic spectrum was identified with 7 cases having moderate to severe intellectual disability and refractory seizures including tonic attacks. Their mean age of onset was 23 months. Three cases had a later age of onset (34 months) with relative preservation of intellect and an initial response to anti-epileptic medication. Conclusions: The phenotypic spectrum of CHD2 encephalopathy has distinctive features of myoclonic epilepsy, marked clinical photosensitivity, atonic-myoclonic-absence seizures and intellectual disability ranging from mild to severe. Recognition of this genetic entity will permit earlier diagnosis, accurate prognostic and genetic counselling for families. Identifying a causative gene is the first step towards targeted biological therapy.